Vesicularization of the endoplasmic reticulum is a fast response to plasma membrane injury

The endoplasmic reticulum of most cell types mainly consists of an extensive network of narrow sheets and tubules. It is well known that an excessive increase of the cytosolic Ca²⁺ concentration induces a slow but extensive swelling of the endoplasmic reticulum into a vesicular morphology. We observed that a similar extensive transition to a vesicular morphology may also occur independently of a change of cytosolic Ca²⁺ and that the change may occur at a time scale of seconds. Exposure of various types of cultured cells to saponin selectively permeabilized the plasma membrane and resulted in a rapid swelling of the endoplasmic reticulum even before a loss of permeability barrier was detectable with a low-molecular mass dye. The structural alteration was reversible provided the exposure to saponin was not too long. Mechanical damage of the plasma membrane resulted in a large-scale transition of the endoplasmic reticulum from a tubular to a vesicular morphology within seconds, also in Ca²⁺-depleted cells. The rapid onset of the phenomenon suggests that it could perform a physiological function. Various mechanisms are discussed whereby endoplasmic reticulum vesicularization could assist in protection against cytosolic Ca²⁺ overload in cellular stress situations like plasma membrane injury.